4,5-dihydroxypyrimidine carboxamides and N-alkyl-5-hydroxypyrimidinone carboxamides are potent, selective HIV integrase inhibitors with good pharmacokinetic profiles in preclinical species

被引：83

作者：

Summa, Vincenzo

Petrocchi, Alessia

Matassa, Victor G.

Gardelli, Cristina

Muraglia, Ester

Rowley, Michael

Paz, Odalys Gonzalez

Laufer, Ralph

Monteagudo, Edith

Pace, Paola

机构：

[1] IRBM MRL Rome, Dept Med Chem, I-00040 Monte Porzio Catone, Italy

[2] IRBM MRL Rome, Dept Drug Metab, I-00040 Monte Porzio Catone, Italy

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2006年 / 49卷 / 23期

关键词：

D O I：

10.1021/jm060854f

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The dihydroxypyrimidine carboxamide 4a was discovered as a potent and selective HIV integrase strand transfer inhibitor. The optimization of physicochemical properties, pharmacokinetic profiles, and potency led to the identification of 13 in the dihydroxypyrimidine series and 18 in the N-methylpyrimidinone series having low nanomolar activity in the cellular HIV spread assay in the presence of 50% normal human serum and very good pharmacokinetics in preclinical species.

引用

页码：6646 / 6649

页数：4

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